Dozen M, Watanabe K, Hosono M, Hayashi Y
Pharmaceuticals Research Laboratories, Fujirebio, Inc., Tokyo, Japan.
Nihon Yakurigaku Zasshi. 1996 Feb;107(2):79-89. doi: 10.1254/fpj.107.79.
Effect of cilnidipine (CIL) on renal function in SHR were evaluated in comparison with that of nifedipine (NIF) and nicardipine (NIC). In conscious SHR, CIL (3 and 10 mg/kg, p.o.) increased the urine volume, urinary Na+ excretion and urinary Na+/K+ ratio. NIF (3 and 10 mg/kg, p.o.) and NIC (10 mg/kg, p.o.) also increased the urine volume and urinary Na+ excretion, but not the urinary Na+/K+ ratio. In anesthetized SHR, CIL (3 and 10 micrograms/kg, i.v.) and NIF (10 micrograms/kg, i.v.) elevated the renal blood flow (RBF), but NIC did not. CIL (10 micrograms/kg, i.v.) also increased the glomerular filtration rate (GFR), whereas NIF did not. Furthermore, we investigated the effect of these three drugs on endothelin (ET)-induced renal dysfunction in anesthetized SHR. ET (2 micrograms/kg, i.v. +30 ng/kg/min) prolongly reduced RBF, GFR and urine volume by 47, 60 and 48%, respectively. CIL (1-10 micrograms/kg, i.v.) improved the decrease in RBF and urine volume induced by ET as well as NIF and NIC. When blood pressure was lowered to the similar extent among the three drugs in ET-treated SHR, CIL increased the RBF and urine volume compared with the others. NIF and NIC did not affect the reduction in GFR by ET, but CIL (0.3-3 micrograms/kg, i.v.) significantly increased GFR. These results suggest that CIL, NIF and NIC all have natriuretic action and no suppressive action on renal function in SHR. In addition, CIL has an ameliorative effect on renal dysfunction in ET-treated SHR, suggesting that CIL might improve renal dysfunction not only in hypertensive patients but also in those with acute renal failure.
将西尼地平（CIL）与硝苯地平（NIF）和尼卡地平（NIC）相比较，评估其对自发性高血压大鼠（SHR）肾功能的影响。在清醒的SHR中，CIL（3和10mg/kg，口服）可增加尿量、尿钠排泄及尿钠/钾比值。NIF（3和10mg/kg，口服）和NIC（10mg/kg，口服）也可增加尿量和尿钠排泄，但不增加尿钠/钾比值。在麻醉的SHR中，CIL（3和10μg/kg，静脉注射）和NIF（10μg/kg，静脉注射）可提高肾血流量（RBF），但NIC无此作用。CIL（10μg/kg，静脉注射）还可增加肾小球滤过率（GFR），而NIF则不能。此外，我们研究了这三种药物对麻醉的SHR中内皮素（ET）诱导的肾功能障碍的影响。ET（2μg/kg，静脉注射 +30ng/kg/min）可使RBF、GFR和尿量分别长期降低47%、60%和48%。CIL（1 - 10μg/kg，静脉注射）可改善ET诱导的RBF和尿量减少，NIF和NIC也有此作用。在ET处理的SHR中，当三种药物使血压降低至相似程度时，与其他药物相比，CIL可增加RBF和尿量。NIF和NIC不影响ET对GFR的降低，但CIL（0.3 - 3μg/kg，静脉注射）可显著增加GFR。这些结果表明，CIL、NIF和NIC在SHR中均有排钠作用且对肾功能无抑制作用。此外，CIL对ET处理的SHR中的肾功能障碍有改善作用，提示CIL不仅可能改善高血压患者的肾功能障碍，还可能改善急性肾衰竭患者的肾功能障碍。
